Vegetables extracts based on compounds with phenolic or poliphenolic functional groups such as Sennosides are not stable in aqueous solutions in the presence of oxygen. The polymers which are formed cause turbidities and precipitations. This results in a loss of pharmaceutically active material.
In order to avoid these chemical instabilities, some pharmaceutical companies have put on the market pharmaceutical products containing Sennosides as the active substance in the solid form [Example: Pursennid (sugar coated tablets) from Sandoz or Agiolax (granulate) from Madaus (in Germany)] or in semisolid form [Example: Tamarine (jam) from Serono]. In the semisolid form (jam), the Sennosides are present in acid form and not as calcium salts. In the acid form Sennosides are not soluble in water and therefore are protected from the degradation process.
The degradation process of Sennosides in aqueous solution is slow and time-progressive; it increases with the increase of storage temperature. The degradation route of Sennosides involves a preliminary breakdown of glucosidic bonds and, soon thereafter, oxidation and polymerization of dianthrones or from hydrolysis.
On the basis of pharmacological research on senna extract, it has been confirmed that the specific influence on colon motility (laxative effect) of Sennosides must be ascribed to the anthrones or dianthrones and not to their degradation products (oxidized or polymerized products) ##STR1##
A reduction of pharmacological activity has to be expected when the degradation process increases.
The main disadvantage of the available formulations (actually on the market) is poor stability and therefore the short shelf-life period (18 months).
Stability data of the marketed solution (old form), in the form of a representative batch of X-Prep is given in Table 1. (Lot 220)
TABLE 1 __________________________________________________________________________ Lot 220 Time Controls 0 6 months 12 months 18 months 24 months __________________________________________________________________________ Characters Brown syrup, unmodified unmodified unmodified unmodified sweet taste, chocolate smell pH 5.28 5.14 5.16 4.93 4.84 Sennosides 2.149 mg/ml 1.922 mg/ml 1.858 mg/ml 1.826 mg/ml 1.773 mg/ml (Th: 2 mg/ml) (107.45%) (96.10%) (92.90%) (91.30%) (88.65%) __________________________________________________________________________
TABLE 2 __________________________________________________________________________ Stability data on extemporary freshly prepared before analysis solution Time Controls 0 6 months 12 months 18 months 24 months 30 months 36 __________________________________________________________________________ months Characters Brown syrup, comply comply comply comply comply comply sweet taste, chocolate smell pH 5.06 5.18 5.10 5.15 5.38 5.27 5.31 Sennosides 2.0092 mg/ml 2.069 mg/ml 2.048 mg/ml 2.0508 mg/ml 2.058 mg/ml 2.035 mg/ml 2.036 mg/ml (Th: 2 mg/ml) (100.46%) (103.45%) (102.40%) (102.54%) (102.90%) (101.75%) ((101.18%) __________________________________________________________________________